Strategy for the prevention of obesity by the regulation of Lipin1

• Project/Area Number: 23790087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Osaka University
• Principal Investigator: ISHIMOTO Kenji 大阪大学, 医学部附属病院, 特任助教(常勤) (00572984)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Lipin1 / 脂質代謝調節因子 / トリグリセリド生合成 / 脂肪酸酸化 / 肥満 / 細部内局在 / プロテオミクス / ユビキチン-プロテアソーム / ユビキチン―プロテアソーム / タンパク質分解制御 / 細胞内局在 / 免疫沈降法

Research Abstract

We set out to search for novel mechanisms for regulation of Lipin1 protein by using proteomics analysis. As a result, we have identified the glycolysis protein, the ubiquitin-proteasome protein, and the proline biosynthetic protein as novel Lipin1 interacting factors. We next examined interaction between Lipin1 and the ubiquitin-proteasome protein actually, and to reveal the proteolytic mechanism for Lipin1. Our findings suggest that Lipin1 is polyubiqutinated by the ubiquitin-proteasome protein, and degraded by ubiquitin-proteasome system.

Research Products

• [Journal Article] Transcriptional activation of low-density lipoprotein receptor gene by DJ-1 and effect of DJ-1 on cholesterol homeostasis (2012)
  • Author(s): Yamaguchi, S., Yamane, T., Takahashi-Niki, K., Kato, I., Niki, T., Goldberg, M. S., Shen, J., Ishimoto, K., Doi, T., Iguchi-Ariga, S. M. M., Ariga, H.
  • Journal Title: PLoS ONE Volume: 7 Issue: 5 Pages: e38144-e38144
  • DOI: 10.1371/journal.pone.0038144
  • Peer Reviewed
• [Journal Article] Lipin 1 in lipid metabolism. (2011)
  • Author(s): Ishimoto K.
  • Journal Title: Yakugaku Zasshi Volume: 131(8) Pages: 1189-1194
  • NAID: 130001075907
  • Peer Reviewed
• [Journal Article] Fenofibrate suppresses growth of the human hepatocellular carcinoma cell via PPARα-independent mechanisms. (2011)
  • Author(s): Yamasaki D, Kawabe N, Nakamura H, Tachibana K, Ishimoto K, Tanaka T, Aburatani H, Sakai J, Hamakubo T, Kodama T, Doi T.
  • Journal Title: Eur. J. Cell Biol. Volume: 90(8) Pages: 657-664
  • Peer Reviewed
• [Journal Article] Fenofibrate suppresses growth of the human hepatocellular carcinoma cell via PPARα-independent mechanisms (2011)
  • Author(s): Daisuke Yamasaki
  • Journal Title: Eur. J. Cell Biol. Volume: 90 Pages: 657-664
  • Peer Reviewed
• [Journal Article] Human mannose-binding lectin 2 is directly regulated by peroxisome proliferator-activated receptors (PPARs) via a peroxisome proliferator responsive element.
  • Author(s): Tachibana K, Takeuchi K, Inada H, Sugimoto K, Ishimoto K, Yamashita M, Maegawa T, Yamasaki D, Osada S, Tanaka T, Rakugi H, Hamakubo T, Sakai J, Kodama T, Doi T.
  • Journal Title: J. Biochem. Volume: (in press)
  • Peer Reviewed
• [Presentation] 核内受容体 PPARδの恒常的転写活性化領域への結合因子の解析 (2013)
  • Author(s): 藤田泰聖,樋野展正,上原光太郎,前川貴志,熊谷文子,石本憲司,橘敬祐,土井健史
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Presentation] 脂質代謝調節因子Lipin1 タンパク質の分解制御機構の解析 (2012)
  • Author(s): 熊谷文子,石本憲司,河井恵,橘敬祐,川村猛,田中十志也,浜窪隆雄,酒井寿郎,児玉龍彦,土井健史
  • Organizer: 第35回 日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] ヒト核内受容体 PPARαによる生体防御レクチン MBL2 の発現制御機構の解析 (2012)
  • Author(s): 橘敬祐,竹内健太郎,稲田大彦,杉本研,石本憲司,田中十志也,楽木宏実,浜窪隆雄,酒井寿郎,児玉龍彦,沢村達也,土井健史
  • Organizer: 第121回 日本薬理学会近畿支部会
  • Place of Presentation: 徳島
• [Presentation] 脂質代謝因子 Lipin1の細胞内局在を制御する相互作用因子の探索 (2011)
  • Author(s): 河井恵,石本憲司,橘敬祐,山崎大典,川村猛,田中十志也,浜窪隆雄,酒井寿郎,児玉龍彦,土井健史
  • Organizer: 第34回 日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 転写制御因子を介したミトコンドリアの脂肪酸酸化制御の解析 (2011)
  • Author(s): 山下雅礼,橘敬祐,杉本研,秋山恵麻,石本憲司,山崎大典,岩成宏子,田中十志也,望月康弘,楽木宏実,酒井寿郎,浜窪隆雄,児玉龍彦,土井健史
  • Organizer: 第34回 日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Global proteomic analysis of lipin1 involved in lipid metabolism (2011)
  • Author(s): Kenji Ishimoto, Megumi Kawai, Keisuke Tachibana, Daisuke Yamasaki, Takefumi Doi
  • Organizer: The 4th Global COE International Symposium on Physiome and Systems Biology for Integrated Life Sciences and Predictive Medicine
  • Place of Presentation: Osaka
• [Presentation] Functional analysis of the roles of posttranslational modification of PPAR delta in regulating transcriptional activity. (2011)
  • Author(s): Keisuke Tachibana, Kotaro Uehara, Takashi Maegawa, Masanori Yamashita, Fumiko Kumagai, Taisei Fujita, Kenji Ishimoto, Daisuke Yamasaki, Takefumi Doi.
  • Organizer: The 4th Global COE International Symposium on Physiome and Systems Biology for Integrated Life Sciences and Predictive Medicine
  • Place of Presentation: Osaka
• [Presentation] Protein purification and generation of antibody for structure analysis of SETDB1. (2011)
  • Author(s): Eiko Gotoh, Keisuke Tachibana, Yoshie Uchihara, Natsuko Kawamata, Kenji Ishimoto, Daisuke Yamasaki, Takefumi Doi.
  • Organizer: The 4th Global COE International Symposium on Physiome and Systems Biology for Integrated Life Sciences and Predictive Medicine
  • Place of Presentation: Osaka
• [Presentation] 肥満解消を目指した Lipin1 遺伝子の発現制御機構の解明 (2011)
  • Author(s): 石本憲司,中村太樹,河井恵,橘敬祐,土井健史
  • Organizer: 第61回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸
• [Presentation] ヒストンメチル化酵素 SETDB1 の細胞内局在の解析 (2011)
  • Author(s): 後藤英子,橘敬祐,内原佳恵,川又那津子,石本憲司,岩成宏子,川村猛,望月康弘,酒井寿郎,浜窪隆雄,児玉龍彦,土井健史
  • Organizer: 第84回 日本生化学会年会
  • Place of Presentation: 京都
• [Presentation] ヒストンメチル化酵素 SETDB1 はメチル基供与体 SAM の輸送体になり得るか? (2011)
  • Author(s): 橘敬祐,後藤英子,内原佳恵,川又那津子,石本憲司,山崎大典,岩成宏子,望月康弘,酒井寿郎,浜窪隆雄,児玉龍彦,土井健史
  • Organizer: 第6回 トランスポーター研究会年会
  • Place of Presentation: 仙台
• [Presentation] 肥満解消を目指したLipin1遺伝子の発現制御機構の解明 (2011)
  • Author(s): 石本 憲司
  • Organizer: 第61回日本薬学会近畿支部総会・大会
  • Place of Presentation: 神戸
• [Presentation] Global proteomic analysis of lipin1 involved in lipid metabolism (2011)
  • Author(s): Kenji Ishimoto
  • Organizer: The 4th Global COE International Symposium on Physiome and Systems Biology for Integrated Life Sciences and Predictive Medicine
  • Place of Presentation: 大阪
• [Presentation] 脂質代謝因子Lipin1の細胞内局在を制御する相互作用因子の探索 (2011)
  • Author(s): 河井 恵
  • Organizer: 第34回 日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 脂質代謝調節因子Lipin1タンパク質の分解制御機構の解析
  • Author(s): 熊谷文子
  • Organizer: 第35回 日本分子生物学会年会
  • Place of Presentation: 福岡
• [Presentation] ヒト核内受容体PPARαによる生体防御レクチンMBL2の発現制御機構の解析
  • Author(s): 橘敬祐
  • Organizer: 第１２１回 日本薬理学会近畿支部会
  • Place of Presentation: 徳島
• [Presentation] 核内受容体PPAR deltaの恒常的転写活性化領域への結合因子の解析
  • Author(s): 藤田泰聖
  • Organizer: 日本薬学会 第133年会
  • Place of Presentation: 横浜
• [Book] 血管生物医学事典(日本血管生物医学会編) (2011)
  • Author(s): 石本憲司,土井健史
  • Publisher: 朝倉書店